1-Methylimidazole → 1,1-dimethylethyl (3R)-3-(cyclopentylmethyl)-4-oxo-4-{5-[(2-pyrimidinylamino)carbonyl]-4,5-dihydro-1H-pyrazol-1-yl}butanoate

HRID 1396966Notes

Reaction equation

CN1C=CN=C1.[CH:7]1([CH2:12][C@H:13]([CH2:24][C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[C:14]([N:16]2[CH:20]([C:21]([OH:23])=O)[CH2:19][CH:18]=[N:17]2)=[O:15])[CH2:11][CH2:10][CH2:9][CH2:8]1.CS(Cl)(=O)=O.[N:37]1[CH:42]=[CH:41][CH:40]=[N:39][C:38]=1[NH2:43]>ClCCl>[CH:7]1([CH2:12][C@@H:13]([C:14](=[O:15])[N:16]2[CH:20]([C:21]([NH:43][C:38]3[N:39]=[CH:40][CH:41]=[CH:42][N:37]=3)=[O:23])[CH2:19][CH:18]=[N:17]2)[CH2:24][C:25]([O:27][C:28]([CH3:30])([CH3:29])[CH3:31])=[O:26])[CH2:11][CH2:10][CH2:9][CH2:8]1

Participants

Conditions

Temperature: 0 °C

Procedure

1-Methyl-1H-imidazole (0.24 mL, 3.0 mmol) was added into a solution of 1-{(2R)-2-(cyclopentylmethyl)-4-[(1,1-dimethylethyl)oxy]-4-oxobutanoyl}-4,5-dihydro-1H-pyrazole-5-carboxylic acid (352 mg, 1.0 mmol) in dichloromethane (DCM) (5.0 mL). The resulting solution was cooled to 0° C., and then methanesulfonyl chloride (0.08 mL, 1.05 mmol) was added dropwise at 0° C. To the reaction mixture was then added 2-pyrimidinamine (105 mg, 1.1 mmol), and stirring continued for 30 min at room temperature. After this time, the solvent was removed under reduced pressure to provide a residue which was purified by Combiflash automated silica gel chromatography (80-100% EtOAc in Hex) to afford 1,1-dimethylethyl (3R)-3-(cyclopentylmethyl)-4-oxo-4-{5-[(2-pyrimidinylamino)carbonyl]-4,5-dihydro-1H-pyrazol-1-yl}butanoate (270 mg, 0.63 mmol, 63% yield). MS: 430 ([M+H]+).

Workup

customAfter this time, the solvent was removed under reduced pressure
customto provide a residue which
customwas purified by Combiflash automated silica gel chromatography (80-100% EtOAc in Hex)

Sources & evidence

ORD record: ord-0140201fc8b94a08b8bda21eca684bda
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08901119B2

Reaction notes

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